Elicitors stimulate paclitaxel production by endophytic fungi isolated from ecologically altered Taxus baccata

The commercial production of paclitaxel; the most potent anti-cancer drug, is based on its extraction from Taxus spp (yews) or microbial fermentation from yews endophytes. The present study investigated the capability of local endophytes that have been isolated from ecologically altered Taxus baccata (host tree) to produce this diterpenoid secondary metabolite and improve its production and stability. Results revealed the ability of three endophytes; Acremonium, Colletotrichum and Fusarium spp, to produce paclitaxel up to 116.19 μgl^-1. The challenge of their production instability away from their host is overcome by two strategies; the addition of unusual elicitor (0.0001% crushed bark of T. baccata) and induction of mutagenesis using ultraviolet irradiation which stimulated the production to higher levels (reach four folds for parent strain Acremonium sp. MK). Produced paclitaxel has a strong cytotoxic effect on human breast cancer cell line (MCF-7). The molecular analysis of the endophyte; Acremonium sp. showed the presence of BAPT gene that responsible for paclitaxel production and encoding C-13 phenylpropanoid side chain-acetyl coenzyme A acetyl-transferase. Therefore, the selected endophyte has an individual metabolic system that can be activated in the absence of the host or changing its ecology